Compulsive-Like Sufentanil Vapor Self-Administration in Rats

Autor: Emily G. Lowery-Gionta, Janaina C. M. Vendruscolo, Stephanie A. Carmack, Maury Cole, Brooke E. Schmeichel, Olivier George, George F. Koob, Brendan J. Tunstall, Leandro F. Vendruscolo, Sophia A. Vandewater, Michael A. Taffe
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Sufentanil
Narcotic Antagonists
Wistar
Self Administration
Pharmacology
Medical and Health Sciences
Substance Misuse
0302 clinical medicine
Medicine
Prescription Drug Abuse
Psychiatry
Analgesics
Inhalation
Naloxone
Drug Abstinence
Analgesics
Opioid
Psychiatry and Mental health
Anesthesia
Compulsive behavior
Administration
Compulsive Behavior
Original Article
Drug
medicine.symptom
Self-administration
medicine.drug
Opioid
Dose-Response Relationship
Operant
03 medical and health sciences
Administration
Inhalation
Animals
Inverse agonist
Rats
Wistar
Dose-Response Relationship
Drug
business.industry
Prevention
Psychology and Cognitive Sciences
Neurosciences
Brain Disorders
Rats
Good Health and Well Being
030104 developmental biology
Conditioning
Operant
Volatilization
Drug Abuse (NIDA only)
business
030217 neurology & neurosurgery
Conditioning
Zdroj: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, vol 43, iss 4
ISSN: 1740-634X
0893-133X
DOI: 10.1038/npp.2017.172
Popis: Opioid misuse is at historically high levels in the United States, with inhalation (ie, smoking and vaping) being one of the most common routes of consumption. We developed and validated a novel preclinical model of opioid self-administration by inhalation that does not require surgery and reliably produces somatic and motivational signs of dependence. Rats were trained to perform an operant response (nosepoke) to receive 10 s of vaporized sufentanil, a potent opioid, in 2 h daily sessions. Rats readily and concentration-dependently self-administered vaporized sufentanil. Rats exhibited a significant increase in responding for sufentanil when given the preferential μ-opioid receptor inverse agonist naloxone, suggesting the participation of μ-opioid receptors in the reinforcing properties of sufentanil vapor. Serum sufentanil concentrations significantly correlated with the number of sufentanil vapor deliveries. Rats that were given long access (LgA; 12 h/day) but not short access (ShA; 1 h/day) to vaporized sufentanil escalated their drug intake over time and exhibited both naloxone-precipitated somatic signs of opioid withdrawal and spontaneous withdrawal-induced mechanical hypersensitivity. After 6 months of forced drug abstinence, LgA rats returned to pre-escalation baseline levels of responding for sufentanil and mechanical sensitivity. Upon subsequent re-escalation (ie, after the return to extended access to sufentanil vapor), LgA rats again developed naloxone-precipitated somatic signs of withdrawal and spontaneous withdrawal-induced mechanical hypersensitivity. These findings demonstrate that the operant sufentanil vapor self-administration model has both face and construct validity and therefore will be useful for investigating the neurobiological basis of opioid addiction.
Databáze: OpenAIRE
Externí odkaz: